No abstract

We have identified a new role for the matrix enzyme lysyl oxidase-like-2 (LOXL2) in the creation and maintenance of the pathologic microenvironment of cancer and fibrotic disease. Our analysis of biopsies from human tumors and fibrotic lung and liver tissues revealed an increase in LOXL2 in disease-associated stroma and limited expression in healthy tissues. Targeting LOXL2 with an inhibitory monoclonal antibody (AB0023) was efficacious in both primary and metastatic xenograft models of cancer, as well as in liver and lung fibrosis models. Inhibition of LOXL2 resulted in a marked reduction in activated fibroblasts, desmoplasia and endothelial cells, decreased production of growth factors and cytokines and decreased transforming growth factor-beta (TGF-beta) pathway signaling. AB0023 outperformed the small-molecule lysyl oxidase inhibitor beta-aminoproprionitrile. The efficacy and safety of LOXL2-specific AB0023 represents a new therapeutic approach with broad applicability in oncologic and fibrotic diseases.

The study was supported by Novartis.

Sevoflurane preconditioning preserves myocardial and renal function as assessed by biochemical markers in patients undergoing coronary artery bypass graft surgery under cardioplegic arrest. This study demonstrated for the first time translocation of protein kinase C isoforms delta and epsilon in human myocardium in response to sevoflurane.

The terminology surrounding basosquamous carcinoma is confusing and there is a need for more uniform language. Based on our review and personal experience, we propose a more precise and specific definition. Data regarding the incidence, recurrence, and metastasis rates of basosquamous carcinoma are based mostly on retrospective series with a limited number of cases. We conclude that although the incidence of basosquamous carcinoma is unknown, there is a literature precedent suggesting more aggressive biological behavior. We believe that complete surgical excision is the preferred approach, and that basosquamous carcinoma is an ideal candidate lesion for Mohs micrographic surgery.